卡培他滨致小鼠手足综合征模型的建立及评价  

Establishment of mouse model of hand-foot syndrome induced by capecitabine

作　　者：王鹏 陈顺 赵逸 高守红 王志鹏 WANG Peng;CHEN Shun;ZHAO Yi;GAO Shouhong;WANG Zhipeng(Department of Pharmacy,Second Affiliated Hospital,Naval Medical University,Shanghai 200003,China;Shanghai Guard District Yangpu Fifth Demobilized Cadres Retreat Outpatient Department,Shanghai 200003,China)

机构地区：[1]海军军医大学第二附属医院药剂科,上海200003 [2]上海警备区杨浦第五离职干部休养所门诊部,上海200003

出　　处：《药学实践与服务》2024年第9期385-388,398,共5页Journal of Pharmaceutical Practice and Service

基　　金：国家自然科学基金项目(82204819);上海市卫生健康委员会青年项目(20214Y0319);上海长征医院"金字塔人才工程"优秀青年医师项目A类(YQ672)。

摘　　要：目的手足综合征是卡培他滨的剂量限制性毒性反应。目前手足综合征模型的建立并没有统一的金标准,本实验给予ICR小鼠灌胃卡培他滨,诱导手足综合征发生,为手足综合征模型的建立提供借签。方法42只雄性ICR小鼠随机分为对照组(6只)和实验组(36只),实验组持续2周灌胃给予卡培他滨(275 mg/kg,2次/d),对照组给予溶剂0.5%CMCNa(4 ml/kg,2次/d),取小鼠足部皮肤样本进行H&E染色,观察足跖部特征性外观以及形态改变,评估手足综合征的动物模型是否成功构建;实验结束后处死小鼠,收集血浆,定量其中卡培他滨及其代谢产物浓度改变。结果6只对照组小鼠均未出现手足综合征症状;实验组19只小鼠足部皮肤出现红斑、肿胀等症状,H&E染色可见部分足底皮肤角表皮层增厚,部分角质脱失破损,判断为发生手足综合征。发生与未发生手足综合征小鼠血浆中卡培他滨及其代谢产物浓度未见明显差异。结论卡培他滨致小鼠手足综合征的模型构建成功;卡培他滨及其代谢产物体内暴露水平差异可能不是手足综合征发生的原因。Objective Hand-foot syndrome is a dose-limiting toxicity of capecitabine.At present,there is no unified gold standard for the establishment of hand-foot syndrome model.To induce hand-foot syndrome and provide a reference for the establishment of hand-foot syndrome model by administering capecitabine in ICR mice.Methods 42 male ICR mice were randomly divided into control group(6 mice)and experimental group(36 mice).The experimental group was given capecitabine(275 mg/kg,twice/d)by intragastric administration for two weeks,and the control group was given 0.5%CMC-Na(4 ml/kg,twice/d),to evaluate whether the animal model of hand-foot syndrome was successfully constructed through H&E staining of mouse foot skin samples and observe morphological changes and the characteristic appearance of mouse foot skin.After the experiment,the mice were sacrificed,and plasma was collected to quantify the concentrations of capecitabine and metabolites.Results Control mice did not showed symptoms of hand-foot syndrome.The skin of the feet of 19 mice in the experimental group showed symptoms such as erythema and swelling,and H&E staining results showed that the plantar skin angular epidermis was thickened,and part of the keratin was exfoliated and damaged,which was considered to be hand-foot syndrome.There were no significant differences in the concentrations of capecitabine and its metabolites between mice with and without hand-foot syndrome.Conclusion The model of hand-foot syndrome induced by capecitabine in mice was successfully established.Differences in exposure levels of capecitabine and metabolites may not be the cause of hand-foot syndrome.

关 键 词：卡培他滨 手足综合征 模型 药物浓度 ICR小鼠 

分 类 号：R965[医药卫生—药理学]